Open-Angle Glaucoma, Ocular Hypertension
Conditions
Keywords
open-angle glaucoma, ocular hypertension, OAG, OHT
Brief summary
The purpose of this study was to evaluate the safety and efficacy of Brinzolamide/Brimonidine fixed combination in lowering intraocular pressure (IOP) relative to each of its individual active constituents instilled concomitantly (Brinzolamide+Brimonidine) in patients with open-angle glaucoma or ocular hypertension.
Detailed description
This study consisted of 7 visits conducted during 2 sequential phases: the screening/eligibility phase, which included a screening visit and 2 eligibility visits, and a treatment phase, which included 4 on-therapy visits conducted at Week 2, Week 6, Month 3, and Month 6 (or early exit). Following washout of any IOP-lowering medication, subjects who met all inclusion/exclusion criteria at both eligibility visits and who had IOP measurements within the specified range during this period were randomized to 1 of 2 study drug groups: Brinz/Brim or Brinz+Brim.
Interventions
DRUGBrinzolamide 1%/brimonidine tartrate 0.2% fixed combination ophthalmic suspension
DRUGVehicle
Inactive ingredients used as a placebo for masking purposes
Sponsors
Alcon Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with open-angle glaucoma or ocular hypertension and, in the opinion of the Investigator, are insufficiently controlled on monotherapy or are currently on multiple IOP-lowering medications. * Meet qualifying IOP entry criteria. * Able to understand and sign an informed consent form. * Other protocol-specified inclusion criteria may apply.
Exclusion criteria
* Women of childbearing potential if pregnant, test positive for pregnancy at Screening visit, breastfeeding, or not in agreement to use adequate birth control methods to prevent pregnancy throughout the study. * Severe central visual field loss. * Can not safely undergo the initial washout period and discontinue use of all IOP-lowering ocular medication(s) for the minimum specified period prior to Eligibility Visit 1. * Best corrected visual acuity (BCVA) score worse than 55 ETDRS letters (20/80 Snellen equivalent). * Chronic, recurrent or severe inflammatory eye disease. * Ocular trauma within the preceding 6 months. * Ocular infection or inflammation within the preceding 3 months. * Clinically significant or progressive retinal disease. * Other ocular pathology. * Intraocular surgery within the 6 months prior to entry. * Ocular laser surgery within the 3 months prior to entry. * Any abnormality preventing reliable applanation tonometry. * Any other conditions which would make the patient, in the opinion of the Investigator, unsuitable for the study. * Recent use of high-dose (\>1 gram daily) salicylate therapy. * Recent, current, or anticipated treatment with any medication that augments adrenergic responses, or precludes use of an alpha-adrenergic agonist. * Other protocol-specified
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Diurnal IOP Change From Baseline at Month 3 | Baseline (Day 1), Month 3 | Mean Diurnal IOP Change from Baseline at Month 3 (ie, the subject IOP change from baseline averaged over the 9 AM and + 2 h time points at Month 3) was measured by Goldmann applanation tonometry. The study drug was instilled approximately 15 minutes after conducting the 9AM IOP measurement. One eye from each subject was chosen as the study eye, and only data for the study eye were used for the efficacy analysis. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). |
Participant flow
Recruitment details
Subjects were recruited from 102 investigational centers in the Asia-Pacific region, Canada, Central and South America, Europe, and the United States.
Pre-assignment details
Of the 1184 enrolled, 294 subjects did not meet inclusion/exclusion criteria and were exited from the study as screen failures prior to randomization. Of the 890 randomized, 2 subjects did not receive study medication. This reporting group includes all randomized subjects who received study medication (888), as treated.
Participants by arm
| Arm | Count |
|---|---|
| Brinz/Brim Vehicle, 1 drop instilled in each eye, followed by Brinzolamide 1%/brimonidine tartrate 0.2% fixed combination ophthalmic suspension, 1 drop instilled in each eye. A 10-minute waiting period separated the instillations. Study drugs were instilled twice a day for 6 months. | 452 |
| Brinz+Brim Brimonidine tartrate 0.2% ophthalmic solution, 1 drop instilled in each eye, followed by Brinzolamide 1% ophthalmic suspension, 1 drop instilled in each eye. A 10-minute waiting period separated the instillations. Study drugs were instilled twice a day for 6 months. | 436 |
| Total | 888 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 48 | 58 |
| Overall Study | Inadequate control of IOP | 4 | 4 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Other | 4 | 1 |
| Overall Study | Subject's decision unrelated to an AE | 9 | 10 |
Baseline characteristics
| Characteristic | Brinz/Brim | Brinz+Brim | Total |
|---|---|---|---|
| Age, Customized <65 years | 227 participants | 211 participants | 438 participants |
| Age, Customized ≥ 65 years | 225 participants | 225 participants | 450 participants |
| Sex: Female, Male Female | 252 Participants | 246 Participants | 498 Participants |
| Sex: Female, Male Male | 200 Participants | 190 Participants | 390 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 452 | 0 / 436 |
| serious Total, serious adverse events | 11 / 452 | 8 / 436 |
Outcome results
Primary
Mean Diurnal IOP Change From Baseline at Month 3
Mean Diurnal IOP Change from Baseline at Month 3 (ie, the subject IOP change from baseline averaged over the 9 AM and + 2 h time points at Month 3) was measured by Goldmann applanation tonometry. The study drug was instilled approximately 15 minutes after conducting the 9AM IOP measurement. One eye from each subject was chosen as the study eye, and only data for the study eye were used for the efficacy analysis. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage).
Time frame: Baseline (Day 1), Month 3
Population: Per Protocol (PP): All subjects who received study medication, satisfied prerandomization inclusion/exclusion criteria, and completed at least 1 scheduled on-therapy study visit. In addition, individual subject visits and data points that did not satisfy the protocol criteria may have been excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brinz/Brim | Mean Diurnal IOP Change From Baseline at Month 3 | -8.5 millimeters of mercury (mmHg) | Standard Error 0.16 |
| Brinz+Brim | Mean Diurnal IOP Change From Baseline at Month 3 | -8.3 millimeters of mercury (mmHg) | Standard Error 0.16 |